Specific binding species, such as antibodies, that are conjugated to a label are routinely employed as reagents for rapid assays in the detection of analytes. One such assay is described in EP0291194A1, incorporated herein by reference. In this assay, a lateral flow porous carrier is provided with a mobilisable particulate-labelled antibody specific to the analyte of interest. It is further provided with a second antibody which is also specific for the analyte but which is immobilised in a detection zone. Analyte binds with the labelled mobilisable antibody to form a first complex which is subsequently captured by the second immobilised antibody in the detection zone. The extent of label present in the detection zone provides an indication of the amount of analyte present in a sample. The label may be a particulate species such as gold and its presence in the detection zone may be detected either visually or optically.
Another method for the detection of a labelled specific binding species is disclosed in U.S. Patent Application Publication No. US2003/0186274-A1, incorporated herein by reference. In this method, the extent or presence of a metal-labelled binding species is detected by dissolving the label in the presence of an oxidising agent, such as a strong acid, to form metal ions. The ions are then deposited onto an electrode surface by electrochemical reduction in the presence of a suitably negative potential. The potential is then varied to reoxidise the metal which then returns to solution, producing a current response. The intensity of this response provides an indication of the amount of metal ions deposited at the electrode surface and hence the amount of label initially present. This type of electroanalytical technique is known as stripping voltammetry and can be used for the measurement of low amounts of metal ions (e.g. parts per million or less). The method may be used to detect the presence or extent of any analyte having a binding specificity for the labelled binding species.
The method of US2003/0186274-A1 is exemplified using gold as the label. However, silver can in many ways be considered to be a better label for use in electrochemical detection, mainly because it is easier to oxidise silver to form silver ions than it is gold. For example, the oxidising agents required for the formation of silver ions from silver are less powerful than those required for forming gold ions from gold and hence more appropriate for use in diagnostic kits.
Although silver is disclosed in US2003/0186274-A1 as a metal particle which can be detected, the methods described therein cannot be used for the electrochemical detection of silver and similar metals in biological samples. This is because the oxidised forms of these metals will react with species found in biological samples, such as blood, plasma and urine, to form insoluble electrochemically-inactive complexes. For example, the concentration of chloride ions in urine is typically 150 mM and therefore any silver ions formed by oxidation will immediately precipitate as AgCl and will thus be prevented from being oxidised at the electrode surface. Similarly, bromide ions and sulphur-containing species such as cysteine also present in biological samples will form insoluble electrochemically-inactive complexes with silver ions.